MIT researchers reveal DNA 'Paste' tech behind latest gene editing … – Endpoints News

MIT sci­en­tists have de­vel­oped a tool that they say can in­sert large gene se­quences where they want in the genome.
In a pa­per pub­lished Thurs­day in Na­ture Biotech­nol­o­gy, MIT fel­lows Omar Abu­dayyeh, Jonathan Gooten­berg and col­leagues de­tail a tech­nol­o­gy they call PASTE, which they say can po­ten­tial­ly be used to in­sert long strands of DNA and treat ge­net­ic dis­eases caused by many dif­fer­ent mu­ta­tions, such as cys­tic fi­bro­sis and Leber con­gen­i­tal amau­ro­sis, a rare eye dis­or­der that caus­es blind­ness.
The tech­nol­o­gy has been li­censed to Tome Bio­sciences — a biotech co-found­ed by the duo back in Feb­ru­ary of 2021 and backed by ARCH, Google’s ven­ture arm, a16z, Long­wood Fund, Po­laris Part­ners and Alexan­dria Ven­ture, which joined af­ter its Se­ries A, ac­cord­ing to a re­cent pitch deck ob­tained by End­points News.
Sana Biotech­nol­o­gy al­so has a stake in the com­pa­ny, ac­cord­ing to an April SEC fil­ing.
Abu­dayyeh and Gooten­berg de­clined to com­ment on Tome. The Wa­ter­town, MA-based biotech is led by CEO Rahul Kakkar and has more than 80 full-time em­ploy­ees as of the third quar­ter of this year, ac­cord­ing to the pitch deck slides.
In the pa­per, the re­searchers ex­plain how they fuse two ex­ist­ing tech­nolo­gies: a prime ed­i­tor, which the Broad’s David Liu pi­o­neered and spun out in­to the start­up Prime Med­i­cine, and an in­te­grase, an en­zyme some virus­es use to in­fect bac­te­ria by in­sert­ing their DNA in­to the host cells.
The idea be­hind the com­bined tech­nolo­gies is that in­te­gras­es on their own aren’t eas­i­ly en­gi­neered to in­sert at any lo­ca­tion be­sides their spe­cif­ic tar­get se­quence, but they’re ca­pa­ble of car­ry­ing big se­quences. Prime ed­i­tors, mean­while, can be en­gi­neered to tar­get and ed­it spe­cif­ic spots, but on­ly in short bits — just enough to stick in a tar­get se­quence for the in­te­grase. By com­bin­ing the two in PASTE, re­searchers can in­sert se­quences as large as 36,000 base pairs, in the spots that they want.
Abu­dayyeh told End­points News that un­like cur­rent gene-edit­ing ap­proach­es, which can on­ly go af­ter sin­gle mu­ta­tions of a dis­ease at once, PASTE could ad­dress many mu­ta­tions at the same time at once by re­plac­ing the whole gene. In ad­di­tion, the tech­nique doesn’t cre­ate a dou­ble-strand­ed break in the DNA, re­duc­ing the risk of un­want­ed in­ser­tions or dele­tions, he said.
In a pa­per pub­lished last De­cem­ber in Na­ture Biotech­nol­o­gy, Liu’s lab de­scribed a sim­i­lar ap­proach. The on­ly dif­fer­ence is that Liu’s lab opt­ed not to fuse all the ma­chin­ery to­geth­er, hav­ing the prime ed­i­tor and in­te­grase work sep­a­rate­ly. In their pa­per, Gooten­berg and Abu­dayyeh re­port high­er ef­fi­cien­cy than Liu’s pa­per did. (A month be­fore the Liu lab’s work was pub­lished in Na­ture Biotech­nol­o­gy, both teams had re­leased pre-prints of their work with­in a day of each oth­er.)
Liu said in an email, “In our lab’s hands the prime ed­i­tor–re­com­bi­nase fu­sion does not on av­er­age work bet­ter than sim­ply ex­press­ing the re­com­bi­nase as a sep­a­rate pro­tein, and in some cas­es, the fu­sions worked less ef­fi­cient­ly than the sep­a­rate­ly ex­pressed pro­teins.”
Both Ki­ran Musunuru, Uni­ver­si­ty of Penn­syl­va­nia pro­fes­sor and Verve Ther­a­peu­tics co-founder, and Sam Stern­berg, Co­lum­bia pro­fes­sor and Prime ad­vi­sor, said that they thought both were sim­i­lar. “Is there a big dif­fer­ence? Prob­a­bly not in the grand scheme of things,” Musunuru said. “I don’t think it mat­ters too much whether it’s two dif­fer­ent pro­teins made sep­a­rate­ly or whether it’s a sin­gle pro­tein. They both seem to work rea­son­ably well.”
Musunuru, who re­search­es the ge­net­ics of heart dis­ease, said he’s been us­ing PASTE in his own lab too, af­ter the preprint was pub­lished last year, though while his lab has got­ten the tech­nol­o­gy to work in cells, it hasn’t got­ten it to work in mice. Verve us­es a form of gene edit­ing called base edit­ing, li­censed from Liu’s oth­er biotech Beam Ther­a­peu­tics.
No­tably, Tome doesn’t have a li­cense with Prime Med­i­cine, which hous­es Liu’s prime edit­ing patents from the Broad, and is not in talks for one, a spokesper­son for Prime Med­i­cine told End­points.
Abu­dayyeh and Gooten­berg em­pha­sized that while they used prime edit­ing in their pa­per, the more gen­er­al PASTE frame­work was not lim­it­ed to prime edit­ing. “Prime is one ex­am­ple, but not the on­ly way to do it,” Gooten­berg said.
Musunuru wasn’t so sure, not­ing that he didn’t see how you could make the tech­nique pro­gram­ma­ble, or tar­getable, “with­out some­thing very sim­i­lar to prime edit­ing.”
Abu­dayyeh and Gooten­berg are alum­ni of CRISPR pi­o­neer Feng Zhang’s lab. They’ve launched sev­er­al biotechs, in­clud­ing Sher­lock Bio­sciences and Proof Di­ag­nos­tics, both di­ag­nos­tics com­pa­nies they co-found­ed with Zhang and oth­ers, and Mo­ment Bio­sciences, a stealth com­pa­ny that is de­vel­op­ing “pre­ci­sion mi­cro­bio­me ther­a­py,” ac­cord­ing to a Mass­a­chu­setts cor­po­rate fil­ing. And then, of course, there’s Tome.
The in­dus­try is pay­ing a lot of at­ten­tion and mon­ey to the next it­er­a­tions of CRISPR. Prime launched last year with $315 mil­lion and raised $175 mil­lion when it went pub­lic in Oc­to­ber. Then there’s Tessera, which in Au­gust raised $300 mil­lion, putting its to­tal funds raised over the $500 mil­lion mark. In Feb­ru­ary, In­tel­lia, which is us­ing CRISPR to ed­it genes di­rect­ly in the body, bought for $45 mil­lion cash lit­tle-known Rewrite Ther­a­peu­tics, which its in­vestor called “kind of CRISPR 2.0,” a moniker ap­plied to the likes of base and prime edit­ing, though lit­tle else was said of its tech­nol­o­gy.
Re­searchers are still in the ear­ly days of turn­ing such a tech­nol­o­gy in­to a com­mer­cial ther­a­py — prime edit­ing has nev­er been used in hu­mans. In Abu­dayyeh and Gooten­berg’s pa­per, they were able to get the DNA they want­ed in­to a mouse’s liv­er cells less than 3% of the time. Musunuru said that there was a lot of space for im­prove­ment, not­ing that they would have to get to around at least 10% to have some ther­a­peu­tic ef­fect.
In the pitch deck, Tome says it hopes to be in the clin­ic by 2026.
Ed­i­tors note: This sto­ry was cor­rect­ed to re­move a ref­er­ence to the time­line of re­search by Liu’s team, and a line was added to clar­i­fy the tim­ing of when preprints from each team were pub­lished.
The Asia Pacific region, which has more than 6,772 trial sites each with access to an average of 2,136 million people, has considerable underutilized capacity presenting an opportunity for growth in multinational trials in the region. 
Demand for Asia Pacific trial sites is strong with almost half of the more than 27,000 clinical trials initiated in 2021 having in Asia Pacific, according to the latest analysis from GlobalData in a new report titled State of the Global Biotech Landscape: Where the Opportunities Lie.
Drug pricing watchdog ICER said that the uncertainty in the health benefits of two potential Alzheimer’s drugs makes it challenging to assess their future cost-effectiveness, according to a draft report released Thursday morning.
The report evaluates Biogen and Eisai’s lecanemab and Eli Lilly’s donanemab, both of which are amyloid-clearing antibody drugs due for FDA decisions in the coming weeks and months. The FDA’s deadline for a decision on lecanemab’s accelerated approval is Jan. 6, while the deadline for donanemab is estimated to be in February.
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Just ahead of what would have been his second anniversary as chief financial officer at MorphoSys, Sung Lee put out word that he is exiting the German biotech and headed back to the US.
The biotech says that Lee will be returning to California — for personal reasons.
Lee’s tenure at MorphoSys has been eventful. He’s been given credit for playing a major role in the Constellation buyout just months after his arrival, which delivered pelabresib (CPI-0610), billed at the time as a potential first and best-in-class BET inhibitor, and CPI-0209, a second-generation EZH2 inhibitor.
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Vaxcyte will pay Sutro Biopharma as much as $157.5 million to take over the manufacturing and future development of the cell-free extract used for its vaccine candidates.
Under the agreement, Vaxcyte is paying $22.5 million upfront for the option to work with a contract manufacturer to make the cell-free extract and to develop it further. If it exercises the option, it will pay $75 million, plus as much as $60 million in additional milestone payments.
Two psychiatric-based drug development companies, Vistagen and Pherin Pharmaceuticals, are merging in a deal worth 12.4 million shares and a “nominal amount” of cash, Vistagen announced Wednesday.
According to SEC filings, Vistagen has estimated that the amount of cash will be under $50,000. Vistagen has also agreed to pay Pherin’s merger-related fees up to $325,000.
By acquiring Pherin, Vistagen will take over the company’s existing drug pipeline, including two advanced products and three in the early clinical stage. Vistagen focuses on disorders like anxiety and depression, while Pherin develops neuroactive steroids, known as pherine compounds, for neuropsychiatric and neuroendocrine conditions.
Despite a year littered with setbacks, ProQR Therapeutics is closing 2022 on a high note.
The Dutch biotech is expanding its RNA editing collaboration with Eli Lilly, with a potentially large payoff down the line, the companies announced early Thursday morning.
Lilly is putting down $75 million in upfront cash and equity, with a $50 million option to expand the deal further in the future. There’s also now $3.75 billion in biobucks on the table, compared with $1.25 billion when the pair signed their original deal in September 2021.
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While all has gone quiet on the M&A rumor front for Seagen, one of the pioneers in antibody-drug conjugates, Merck has been racking up deal after deal for ADCs out of a Chengdu, China-based partner.
In the latest of three tie-ups with Kelun-Biotech, Merck is likely entering the history books with a deal that could balloon to $9.3 billion in back-end payments — that’s if seven ADCs make it to market. That’s a huge if, as drug R&D is notorious for an approximately 10% success rate, but the immediate boost to Kelun’s coffers is not small: $175 million plus an intended equity investment of undisclosed size.
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Biology tools company Berkeley Lights will acquire IsoPlexis in a $57.8 million all-stock transaction agreement announced Wednesday. The new company will be named PhenomeX, with Berkeley Lights shareholders owning about 75% and IsoPlexis holders the rest.
Berkeley Lights CEO Siddhartha Kadia will be the CEO of the new company and a member of the board of directors. IsoPlexis CEO Sean Mackay will stay on as chief product officer of PhenomeX.
Enveda Biosciences will enter the clinic next year with at least one of its three main programs thanks to a $68 million boost in financing — about $55 million via equity and the remainder debt.
Founded by an early employee at AI startup Recursion Pharmaceuticals, Enveda has adjusted its priorities since disclosing a $51 million Series A in June 2021. At the time, CEO Viswa Colluru told Endpoints News the three core areas were Wilson disease, NASH and Parkinson’s.
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